Randomized, 3 arms. 518/547 patients. Stage III or IV cancers of the glottic or supraglottic larynx, which would require total laryngectomy. Excluded T1 and large volume T4 (penetrating through cartilage or >1cm into BOT). Arm 1) Induction cisplatin 100 mg/m2 + 5-FU C.I. 1000 mg/m2 Q3W x3 cycles, followed by RT (if CR or PR) or laryngectomy if poor response (this Arm based on results of the VA Larynx trial) vs. Arm 2) Concurrent cisplatin 100 mg/m2 Q3W + RT vs. Arm 3) RT alone. RT dose was 70/35, elective neck and SCV 50/25. Patient in the first arm who had salvage surgery for poor response to chemo received adjuvant RT to 50-70 Gy depending on surgical margin status. Planned lymph node dissection was performed for LN > 3cm or multiple lymph nodes at original staging. In induction group, 83% continued to RT and most of others received more chemotherapy or RT but not surgery. End point was preservation of larynx

Larynx preservation: induction 72% (SS) vs. concurrent 84% vs. RT alone 67% (SS). No benefit to induction chemo over RT alone. Laryngectomy-free survival at 2-years and 5-years was 59%/43% (induction), 66%/45% (concurrent), and 53%/38% (RT alone), with no S.S. difference between the two chemo groups but a S.S. difference between concurrent and RT alone. There was no difference in LFS between the two chemo arms due to an increase in intercurrent deaths for the concomitant group.

Randomized, 3 arms. 518/547 patients. Stage III or IV cancers of the glottic or supraglottic larynx, which would require total laryngectomy. Excluded T1 and large volume T4 (penetrating through cartilage or >1cm into BOT). Arm 1) Induction cisplatin 100 mg/m2 + 5-FU C.I. 1000 mg/m2 Q3W x3 cycles, followed by RT (if CR or PR) or laryngectomy if poor response (this Arm based on results of the VA Larynx trial) vs. Arm 2) Concurrent cisplatin 100 mg/m2 Q3W + RT vs. Arm 3) RT alone. RT dose was 70/35, elective neck and SCV 50/25. Patient in the first arm who had salvage surgery for poor response to chemo received adjuvant RT to 50-70 Gy depending on surgical margin status. Planned lymph node dissection was performed for LN > 3cm or multiple lymph nodes at original staging. In induction group, 83% continued to RT and most of others received more chemotherapy or RT but not surgery. End point was preservation of larynx

Larynx preservation: induction 72% (SS) vs. concurrent 84% vs. RT alone 67% (SS). No benefit to induction chemo over RT alone. Laryngectomy-free survival at 2-years and 5-years was 59%/43% (induction), 66%/45% (concurrent), and 53%/38% (RT alone), with no S.S. difference between the two chemo groups but a S.S. difference between concurrent and RT alone. There was no difference in LFS between the two chemo arms due to an increase in intercurrent deaths for the concomitant group.